Skip to main content
SpringerLink
Log in

ROS-Mediated Apoptosis in Cancer

  • Reference work entry
  • First Online:
Handbook of Oxidative Stress in Cancer: Mechanistic Aspects

  • 77 Accesses

Abstract

Redox homeostasis is defined as a balance between reactive oxygen species (ROS) production and ROS elimination. Intracellular ROS are produced during endoplasmic reticulum (ER) stress, oxidative phosphorylation of mitochondria and by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) family members. ROS are eliminated by antioxidant enzymes such as superoxide dismutase, catalase, and peroxiredoxins as well as by nonenzymatic antioxidants. Moderate levels of ROS activate signaling pathways for cancer cell proliferation and survival, whereas high levels of ROS trigger apoptotic signals. Redox imbalance in cancer cells toward accelerated ROS production makes them more vulnerable to oxidative stress-mediated apoptosis. Therefore, pro-oxidative molecules are exploited for the development of anticancer drugs. In this chapter, we discuss ROS-induced (i) mitochondria-, (ii) death receptor-, (iii) p53-, (iv) ER stress-, and (v) calcium-mediated apoptotic pathways in cancer. We also discuss (vi) prooxidant-based cancer therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 799.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 1,599.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Adam-Vizi V, Starkov AA (2010) Calcium and mitochondrial reactive oxygen species generation: how to read the facts. J Alzheimer’s Dis: JAD 20(Suppl 2):S413–S426

    Article  Google Scholar 

  • Akao Y, Yamada H, Nakagawa Y (2000) Arsenic-induced apoptosis in malignant cells in vitro. Leuk Lymphoma 37:53–63

    Article  CAS  PubMed  Google Scholar 

  • Alexandre J, Nicco C, Chereau C, Laurent A, Weill B, Goldwasser F et al (2006) Improvement of the therapeutic index of anticancer drugs by the superoxide dismutase mimic mangafodipir. J Natl Cancer Inst 98:236–244

    Article  CAS  PubMed  Google Scholar 

  • Anathy V, Aesif SW, Guala AS, Havermans M, Reynaert NL, Ho YS et al (2009) Redox amplification of apoptosis by caspase-dependent cleavage of glutaredoxin 1 and S-glutathionylation of Fas. J Cell Biol 184:241–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Anelli T, Bergamelli L, Margittai E, Rimessi A, Fagioli C, Malgaroli A et al (2012) Ero1alpha regulates Ca(2+) fluxes at the endoplasmic reticulum-mitochondria interface (MAM). Antioxid Redox Signal 16:1077–1087

    Article  CAS  PubMed  Google Scholar 

  • Antman KH (2001) Introduction: the history of arsenic trioxide in cancer therapy. Oncologist 6(Suppl 2):1–2

    Article  CAS  PubMed  Google Scholar 

  • Asumendi A, Morales MC, Alvarez A, Arechaga J, Perez-Yarza G (2002) Implication of mitochondria-derived ROS and cardiolipin peroxidation in N-(4-hydroxyphenyl)retinamide-induced apoptosis. Br J Cancer 86:1951–1956

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Batandier C, Leverve X, Fontaine E (2004) Opening of the mitochondrial permeability transition pore induces reactive oxygen species production at the level of the respiratory chain complex I. J Biol Chem 279:17197–17204

    Article  CAS  PubMed  Google Scholar 

  • Beltran B, Quintero M, Garcia-Zaragoza E, O’Connor E, Esplugues JV, Moncada S (2002) Inhibition of mitochondrial respiration by endogenous nitric oxide: a critical step in Fas signaling. Proc Natl Acad Sci U S A 99:8892–8897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berkenblit A, Eder JP Jr, Ryan DP, Seiden MV, Tatsuta N, Sherman ML et al (2007) Phase I clinical trial of STA-4783 in combination with paclitaxel in patients with refractory solid tumors. Clin Cancer Res 13:584–590

    Article  CAS  PubMed  Google Scholar 

  • Bobrovnikova-Marjon E, Grigoriadou C, Pytel D, Zhang F, Ye J, Koumenis C et al (2010) PERK promotes cancer cell proliferation and tumor growth by limiting oxidative DNA damage. Oncogene 29:3881–3895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen YC, Lin-Shiau SY, Lin JK (1998) Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosis. J Cell Physiol 177:324–333

    Article  CAS  PubMed  Google Scholar 

  • Chou WC, Jie C, Kenedy AA, Jones RJ, Trush MA, Dang CV (2004) Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells. Proc Natl Acad Sci U S A 101:4578–4583

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Choudhary S, Wang KK, Wang HC (2011) Oncogenic H-Ras, FK228, and exogenous H2O2 cooperatively activated the ERK pathway in selective induction of human urinary bladder cancer J82 cell death. Mol Carcinog 50:215–219

    Article  CAS  PubMed  Google Scholar 

  • Chua PJ, Yip GW, Bay BH (2009) Cell cycle arrest induced by hydrogen peroxide is associated with modulation of oxidative stress related genes in breast cancer cells. Exp Biol Med 234:1086–1094

    Article  CAS  Google Scholar 

  • Clement MV, Stamenkovic I (1996) Superoxide anion is a natural inhibitor of FAS-mediated cell death. EMBO J 15:216–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davydov DR (2001) Microsomal monooxygenase in apoptosis: another target for cytochrome c signaling? Trends Biochem Sci 26:155–160

    Article  CAS  PubMed  Google Scholar 

  • Dhanasekaran DN, Reddy EP (2008) JNK signaling in apoptosis. Oncogene 27:6245–6251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dorr RT, Raymond MA, Landowski TH, Roman NO, Fukushima S (2005) Induction of apoptosis and cell cycle arrest by imexon in human pancreatic cancer cell lines. Int J Gastrointest Cancer 36:15–28

    Article  CAS  PubMed  Google Scholar 

  • Dragovich T, Gordon M, Mendelson D, Wong L, Modiano M, Chow HH et al (2007) Phase I trial of imexon in patients with advanced malignancy. J Clin Oncol 25:1779–1784

    Article  CAS  PubMed  Google Scholar 

  • Drane P, Bravard A, Bouvard V, May E (2001) Reciprocal down-regulation of p53 and SOD2 gene expression-implication in p53 mediated apoptosis. Oncogene 20:430–439

    Article  CAS  PubMed  Google Scholar 

  • Du C, Fang M, Li Y, Li L, Wang X (2000) Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition. Cell 102:33–42

    Article  CAS  PubMed  Google Scholar 

  • Dvorakova K, Payne CM, Tome ME, Briehl MM, McClure T, Dorr RT (2000) Induction of oxidative stress and apoptosis in myeloma cells by the aziridine-containing agent imexon. Biochem Pharmacol 60:749–758

    Article  CAS  PubMed  Google Scholar 

  • Dvorakova K, Waltmire CN, Payne CM, Tome ME, Briehl MM, Dorr RT (2001) Induction of mitochondrial changes in myeloma cells by imexon. Blood 97:3544–3551

    Article  CAS  PubMed  Google Scholar 

  • Evens AM (2004) Motexafin gadolinium: a redox-active tumor selective agent for the treatment of cancer. Curr Opin Oncol 16:576–580

    Article  CAS  PubMed  Google Scholar 

  • Evens AM, Prachand S, Shi B, Paniaqua M, Gordon LI, Gartenhaus RB (2004) Imexon-induced apoptosis in multiple myeloma tumor cells is caspase-8 dependent. Clin Cancer Res 10:1481–1491

    Article  CAS  PubMed  Google Scholar 

  • Fan XY, Chen XY, Liu YJ, Zhong HM, Jiang FL, Liu Y (2016) Oxidative stress-mediated intrinsic apoptosis in human promyelocytic leukemia HL-60 cells induced by organic arsenicals. Sci Rep 6:29865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Faraonio R, Vergara P, Di Marzo D, Pierantoni MG, Napolitano M, Russo T et al (2006) p53 suppresses the Nrf2-dependent transcription of antioxidant response genes. J Biol Chem 281:39776–39784

    Article  CAS  PubMed  Google Scholar 

  • Fribley A, Zeng Q, Wang CY (2004) Proteasome inhibitor PS-341 induces apoptosis through induction of endoplasmic reticulum stress-reactive oxygen species in head and neck squamous cell carcinoma cells. Mol Cell Biol 24:9695–9704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gilady SY, Bui M, Lynes EM, Benson MD, Watts R, Vance JE et al (2010) Ero1alpha requires oxidizing and normoxic conditions to localize to the mitochondria-associated membrane (MAM). Cell Stress Chaperones 15:619–629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giorgio M, Migliaccio E, Orsini F, Paolucci D, Moroni M, Contursi C et al (2005) Electron transfer between cytochrome c and p66Shc generates reactive oxygen species that trigger mitochondrial apoptosis. Cell 122:221–233

    Article  CAS  PubMed  Google Scholar 

  • Glasauer A, Sena LA, Diebold LP, Mazar AP, Chandel NS (2014) Targeting SOD1 reduces experimental non-small-cell lung cancer. J Clin Invest 124:117–128

    Article  CAS  PubMed  Google Scholar 

  • Goda AE, Erikson RL, Sakai T, Ahn JS, Kim BY (2015) Preclinical evaluation of bortezomib/dipyridamole novel combination as a potential therapeutic modality for hematologic malignancies. Mol Oncol 9:309–322

    Article  CAS  PubMed  Google Scholar 

  • Gorlach A, Bertram K, Hudecova S, Krizanova O (2015) Calcium and ROS: a mutual interplay. Redox Biol 6:260–271

    Article  PubMed  PubMed Central  Google Scholar 

  • Gulbins E, Brenner B, Schlottmann K, Welsch J, Heinle H, Koppenhoefer U et al (1996) Fas-induced programmed cell death is mediated by a Ras-regulated O2- synthesis. Immunology 89:205–212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hadji A, Ceppi P, Murmann AE, Brockway S, Pattanayak A, Bhinder B et al (2014) Death induced by CD95 or CD95 ligand elimination. Cell Rep 7:208–222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hampton MB, Orrenius S (1997) Dual regulation of caspase activity by hydrogen peroxide: implications for apoptosis. FEBS Lett 414:552–556

    Article  CAS  PubMed  Google Scholar 

  • Hayashi T, Rizzuto R, Hajnoczky G, Su TP (2009) MAM: more than just a housekeeper. Trends Cell Biol 19:81–88

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He Z, Simon HU (2013) A novel link between p53 and ROS. Cell Cycle 12:201–202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hempel N, Trebak M (2017) Crosstalk between calcium and reactive oxygen species signaling in cancer. Cell Calcium 63:70–96

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hileman EO, Liu J, Albitar M, Keating MJ, Huang P (2004) Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity. Cancer Chemother Pharmacol 53:209–219

    Article  CAS  PubMed  Google Scholar 

  • Hu H, Tian M, Ding C, Yu S (2018) The C/EBP homologous protein (CHOP) transcription factor functions in endoplasmic reticulum stress-induced apoptosis and microbial infection. Front Immunol 9:3083

    Article  CAS  PubMed  Google Scholar 

  • Humpton TJ, Vousden KH (2016) Regulation of cellular metabolism and hypoxia by p53. Cold Spring Harb Perspect Med 6

    Google Scholar 

  • Huo H, Zhou Z, Qin J, Liu W, Wang B, Gu Y (2016) Erastin disrupts mitochondrial permeability transition pore (mPTP) and induces apoptotic death of colorectal Cancer cells. PLoS One 11:e0154605

    Article  PubMed  PubMed Central  Google Scholar 

  • Inoue T, Suzuki-Karasaki Y (2013) Mitochondrial superoxide mediates mitochondrial and endoplasmic reticulum dysfunctions in TRAIL-induced apoptosis in Jurkat cells. Free Radic Biol Med 61:273–284

    Article  CAS  PubMed  Google Scholar 

  • Izeradjene K, Douglas L, Tillman DM, Delaney AB, Houghton JA (2005) Reactive oxygen species regulate caspase activation in tumor necrosis factor-related apoptosis-inducing ligand-resistant human colon carcinoma cell lines. Cancer Res 65:7436–7445

    Article  CAS  PubMed  Google Scholar 

  • Jiang X, Wang X (2000) Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1. J Biol Chem 275:31199–31203

    Article  CAS  PubMed  Google Scholar 

  • Jiang J, Huang Z, Zhao Q, Feng W, Belikova NA, Kagan VE (2008) Interplay between bax, reactive oxygen species production, and cardiolipin oxidation during apoptosis. Biochem Biophys Res Commun 368:145–150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jing Y, Dai J, Chalmers-Redman RM, Tatton WG, Waxman S (1999) Arsenic trioxide selectively induces acute promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway. Blood 94:2102–2111

    Article  CAS  PubMed  Google Scholar 

  • Kagan VE, Tyurin VA, Jiang J, Tyurina YY, Ritov VB, Amoscato AA et al (2005) Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol 1:223–232

    Article  CAS  PubMed  Google Scholar 

  • Kagan VE, Bayir HA, Belikova NA, Kapralov O, Tyurina YY, Tyurin VA et al (2009) Cytochrome c/cardiolipin relations in mitochondria: a kiss of death. Free Radic Biol Med 46:1439–1453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kagan VE, Chu CT, Tyurina YY, Cheikhi A, Bayir H (2014) Cardiolipin asymmetry, oxidation and signaling. Chem Phys Lipids 179:64–69

    Article  CAS  PubMed  Google Scholar 

  • Kantari C, Walczak H (1813) Caspase-8 and bid: caught in the act between death receptors and mitochondria. Biochim Biophys Acta 2011:558–563

    Google Scholar 

  • Katagiri K, Matsuzawa A, Ichijo H (2010) Regulation of apoptosis signal-regulating kinase 1 in redox signaling. Methods Enzymol 474:277–288

    Article  CAS  PubMed  Google Scholar 

  • Katoh I, Tomimori Y, Ikawa Y, Kurata S (2004) Dimerization and processing of procaspase-9 by redox stress in mitochondria. J Biol Chem 279:15515–15523

    Article  CAS  PubMed  Google Scholar 

  • Kim EK, Jang M, Song MJ, Kim D, Kim Y, Jang HH (2019) Redox-mediated mechanism of chemoresistance in Cancer cells. Antioxidants 8

    Google Scholar 

  • Kroemer G, de The H (1999) Arsenic trioxide, a novel mitochondriotoxic anticancer agent? J Natl Cancer Inst 91:743–745

    Article  CAS  PubMed  Google Scholar 

  • Krueger A, Baumann S, Krammer PH, Kirchhoff S (2001) FLICE-inhibitory proteins: regulators of death receptor-mediated apoptosis. Mol Cell Biol 21:8247–8254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee WC, Choi CH, Cha SH, Oh HL, Kim YK (2005) Role of ERK in hydrogen peroxide-induced cell death of human glioma cells. Neurochem Res 30:263–270

    Article  CAS  PubMed  Google Scholar 

  • Lei Y, Wang S, Ren B, Wang J, Chen J, Lu J et al (2017) CHOP favors endoplasmic reticulum stress-induced apoptosis in hepatocellular carcinoma cells via inhibition of autophagy. PLoS One 12:e0183680

    Article  PubMed  PubMed Central  Google Scholar 

  • Lemasters JJ, Theruvath TP, Zhong Z, Nieminen AL (1787) Mitochondrial calcium and the permeability transition in cell death. Biochim Biophys Acta 2009:1395–1401

    Google Scholar 

  • Li LY, Luo X, Wang X (2001) Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412:95–99

    Article  CAS  PubMed  Google Scholar 

  • Li G, Mongillo M, Chin KT, Harding H, Ron D, Marks AR et al (2009) Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J Cell Biol 186:783–792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin TS, Naumovski L, Lecane PS, Lucas MS, Moran ME, Cheney C et al (2009) Effects of motexafin gadolinium in a phase II trial in refractory chronic lymphocytic leukemia. Leuk Lymphoma 50:1977–1982

    Article  CAS  PubMed  Google Scholar 

  • Lin J, Zahurak M, Beer TM, Ryan CJ, Wilding G, Mathew P et al (2013) A non-comparative randomized phase II study of 2 doses of ATN-224, a copper/zinc superoxide dismutase inhibitor, in patients with biochemically recurrent hormone-naive prostate cancer. Urol Oncol 31:581–588

    Article  CAS  PubMed  Google Scholar 

  • Liou GY, Storz P (2010) Reactive oxygen species in cancer. Free Radic Res 44:479–496

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Zhu X (2017) Endoplasmic reticulum-mitochondria tethering in neurodegenerative diseases. Transl Neurodegeneration 6:21

    Article  Google Scholar 

  • Liu SL, Lin X, Shi DY, Cheng J, Wu CQ, Zhang YD (2002) Reactive oxygen species stimulated human hepatoma cell proliferation via cross-talk between PI3-K/PKB and JNK signaling pathways. Arch Biochem Biophys 406:173–182

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Jiang CC, Lavis CJ, Croft A, Dong L, Tseng HY et al (2009) 2-Deoxy-D-glucose enhances TRAIL-induced apoptosis in human melanoma cells through XBP-1-mediated up-regulation of TRAIL-R2. Mol Cancer 8:122

    Article  PubMed  PubMed Central  Google Scholar 

  • Lowndes SA, Adams A, Timms A, Fisher N, Smythe J, Watt SM et al (2008) Phase I study of copper-binding agent ATN-224 in patients with advanced solid tumors. Clin Cancer Res 14:7526–7534

    Article  CAS  PubMed  Google Scholar 

  • Lu Z, Xu S (2006) ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life 58:621–631

    Article  CAS  PubMed  Google Scholar 

  • Lu GD, Shen HM, Chung MC, Ong CN (2007a) Critical role of oxidative stress and sustained JNK activation in aloe-emodin-mediated apoptotic cell death in human hepatoma cells. Carcinogenesis 28:1937–1945

    Article  CAS  PubMed  Google Scholar 

  • Lu J, Chew EH, Holmgren A (2007b) Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide. Proc Natl Acad Sci U S A 104:12288–12293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ma Y, Zhang L, Rong S, Qu H, Zhang Y, Chang D et al (2013) Relation between gastric cancer and protein oxidation, DNA damage, and lipid peroxidation. Oxidative Med Cell Longev 2013:543760

    Article  Google Scholar 

  • Magda D, Miller RA (2006) Motexafin gadolinium: a novel redox active drug for cancer therapy. Semin Cancer Biol 16:466–476

    Article  CAS  PubMed  Google Scholar 

  • Magda D, Lepp C, Gerasimchuk N, Lee I, Sessler JL, Lin A et al (2001) Redox cycling by motexafin gadolinium enhances cellular response to ionizing radiation by forming reactive oxygen species. Int J Radiat Oncol Biol Phys 51:1025–1036

    Article  CAS  PubMed  Google Scholar 

  • Maillet A, Pervaiz S (2012) Redox regulation of p53, redox effectors regulated by p53: a subtle balance. Antioxid Redox Signal 16:1285–1294

    Article  CAS  PubMed  Google Scholar 

  • Mao Y, Song G, Cai Q, Liu M, Luo H, Shi M et al (2006) Hydrogen peroxide-induced apoptosis in human gastric carcinoma MGC803 cells. Cell Biol Int 30:332–337

    Article  CAS  PubMed  Google Scholar 

  • McCullough KD, Martindale JL, Klotz LO, Aw TY, Holbrook NJ (2001) Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol 21:1249–1259

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miller RA, Woodburn KW, Fan Q, Lee I, Miles D, Duran G et al (2001) Motexafin gadolinium: a redox active drug that enhances the efficacy of bleomycin and doxorubicin. Clin Cancer Res 7:3215–3221

    CAS  PubMed  Google Scholar 

  • Min SK, Lee SK, Park JS, Lee J, Paeng JY, Lee SI et al (2008) Endoplasmic reticulum stress is involved in hydrogen peroxide induced apoptosis in immortalized and malignant human oral keratinocytes. J Oral Pathol Med 37:490–498

    Article  CAS  PubMed  Google Scholar 

  • Modica-Napolitano JS, Bharath LP, Hanlon AJ, Hurley LD (2019) The anticancer agent elesclomol has direct effects on mitochondrial bioenergetic function in isolated mammalian mitochondria. Biomol Ther 9

    Google Scholar 

  • Morciano G, Marchi S, Morganti C, Sbano L, Bittremieux M, Kerkhofs M et al (2018) Role of mitochondria-associated ER membranes in calcium regulation in cancer-specific settings. Neoplasia 20:510–523

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moulder S, Dhillon N, Ng C, Hong D, Wheler J, Naing A et al (2010) A phase I trial of imexon, a pro-oxidant, in combination with docetaxel for the treatment of patients with advanced breast, non-small cell lung and prostate cancer. Investig New Drugs 28:634–640

    Article  CAS  Google Scholar 

  • Nakata W, Hayakawa Y, Nakagawa H, Sakamoto K, Kinoshita H, Takahashi R et al (2011) Anti-tumor activity of the proteasome inhibitor bortezomib in gastric cancer. Int J Oncol 39:1529–1536

    CAS  PubMed  Google Scholar 

  • Naumovski LCJ, Sirisawad M, Ramos J, Miller R (2004) Motexafin gadolinium (Xcytrin®) cooperates with other therapeutic agents to kill lymphoma and myeloma tumor cell lines. Proc Amer Assoc Cancer Res 45

    Google Scholar 

  • NavaneethaKrishnan S, Rosales JL, Lee KY (2018) Loss of Cdk5 in breast cancer cells promotes ROS-mediated cell death through dysregulation of the mitochondrial permeability transition pore. Oncogene 37:1788–1804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • NavaneethaKrishnan S, Rosales JL, Lee KY (2019) ROS-mediated cancer cell killing through dietary phytochemicals. Oxidative Med Cell Longev 2019:9051542

    Article  Google Scholar 

  • Newmeyer DD, Ferguson-Miller S (2003) Mitochondria: releasing power for life and unleashing the machineries of death. Cell 112:481–490

    Article  CAS  PubMed  Google Scholar 

  • O’Day SJ, Eggermont AM, Chiarion-Sileni V, Kefford R, Grob JJ, Mortier L et al (2013) Final results of phase III SYMMETRY study: randomized, double-blind trial of elesclomol plus paclitaxel versus paclitaxel alone as treatment for chemotherapy-naive patients with advanced melanoma. J Clin Oncol 31:1211–1218

    Article  PubMed  Google Scholar 

  • Pallepati P, Averill-Bates D (2010) Mild thermotolerance induced at 40 degrees C increases antioxidants and protects HeLa cells against mitochondrial apoptosis induced by hydrogen peroxide: role of p53. Arch Biochem Biophys 495:97–111

    Article  CAS  PubMed  Google Scholar 

  • Pallepati P, Averill-Bates DA (2011a) Activation of ER stress and apoptosis by hydrogen peroxide in HeLa cells: protective role of mild heat preconditioning at 40 degrees C. Biochim Biophys Acta 1813:1987–1999

    Article  CAS  PubMed  Google Scholar 

  • Pallepati P, Averill-Bates DA (2011b) Mild thermotolerance induced at 40 degrees C protects HeLa cells against activation of death receptor-mediated apoptosis by hydrogen peroxide. Free Radic Biol Med 50:667–679

    Article  CAS  PubMed  Google Scholar 

  • Park IJ, Hwang JT, Kim YM, Ha J, Park OJ (2006) Differential modulation of AMPK signaling pathways by low or high levels of exogenous reactive oxygen species in colon cancer cells. Ann N Y Acad Sci 1091:102–109

    Article  CAS  PubMed  Google Scholar 

  • Redza-Dutordoir M, Averill-Bates DA (1863) Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 2016:2977–2992

    Google Scholar 

  • Richard A, Campbell MSG, Betancourt O, Juarez J, Donate F, Mazar A, Berenson JR (2006) ATN-224, an orally available small molecule inhibitor of SOD1, inhibits multiple signaling pathways associated with myeloma progression and has antitumor activity in a murine model of refractory myeloma growth. Proc Amer Assoc Cancer Res:47

    Google Scholar 

  • Rizzuto R, Brini M, Murgia M, Pozzan T (1993) Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria. Science 262:744–747

    Google Scholar 

  • Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM et al (1998) Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science 280:1763–1766

    Article  CAS  PubMed  Google Scholar 

  • Rozpedek W, Pytel D, Mucha B, Leszczynska H, Diehl JA, Majsterek I (2016) The role of the PERK/eIF2alpha/ATF4/CHOP signaling pathway in tumor progression during endoplasmic reticulum stress. Curr Mol Med 16:533–544

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sablina AA, Budanov AV, Ilyinskaya GV, Agapova LS, Kravchenko JE, Chumakov PM (2005) The antioxidant function of the p53 tumor suppressor. Nat Med 11:1306–1313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saitoh M, Nishitoh H, Fujii M, Takeda K, Tobiume K, Sawada Y et al (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J 17:2596–2606

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samulitis BK, Landowski TH, Dorr RT (2006) Correlates of imexon sensitivity in human multiple myeloma cell lines. Leuk Lymphoma 47:97–109

    Article  CAS  PubMed  Google Scholar 

  • Sano R, Reed JC (1833) ER stress-induced cell death mechanisms. Biochim Biophys Acta 2013:3460–3470

    Google Scholar 

  • Sato T, Machida T, Takahashi S, Iyama S, Sato Y, Kuribayashi K et al (2004) Fas-mediated apoptosome formation is dependent on reactive oxygen species derived from mitochondrial permeability transition in Jurkat cells. J Immunol 173:285–296

    Article  CAS  PubMed  Google Scholar 

  • Shen ZY, Shen J, Cai WJ, Hong C, Zheng MH (2000) The alteration of mitochondria is an early event of arsenic trioxide induced apoptosis in esophageal carcinoma cells. Int J Mol Med 5:155–158

    CAS  PubMed  Google Scholar 

  • Shen ZY, Shen WY, Chen MH, Shen J, Cai WJ, Zeng Y (2002) Mitochondria, calcium and nitric oxide in the apoptotic pathway of esophageal carcinoma cells induced by As2O3. Int J Mol Med 9:385–390

    CAS  PubMed  Google Scholar 

  • Shi Y, Nikulenkov F, Zawacka-Pankau J, Li H, Gabdoulline R, Xu J et al (2014) ROS-dependent activation of JNK converts p53 into an efficient inhibitor of oncogenes leading to robust apoptosis. Cell Death Differ 21:612–623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shoeb M, Ansari NH, Srivastava SK, Ramana KV (2014) 4-Hydroxynonenal in the pathogenesis and progression of human diseases. Curr Med Chem 21:230–237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Singh M, Sharma H, Singh N (2007) Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway. Mitochondrion 7:367–373

    Article  CAS  PubMed  Google Scholar 

  • Stridh H, Kimland M, Jones DP, Orrenius S, Hampton MB (1998) Cytochrome c release and caspase activation in hydrogen peroxide- and tributyltin-induced apoptosis. FEBS Lett 429:351–355

    Article  CAS  PubMed  Google Scholar 

  • Sullivan LB, Chandel NS (2014) Mitochondrial reactive oxygen species and cancer. Cancer Metabolism 2:17

    Article  PubMed  PubMed Central  Google Scholar 

  • Susin SA, Lorenzo HK, Zamzami N, Marzo I, Snow BE, Brothers GM et al (1999) Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397:441–446

    Article  CAS  PubMed  Google Scholar 

  • Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R (2001) A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell 8:613–621

    Article  CAS  PubMed  Google Scholar 

  • Suzuki-Karasaki Y, Suzuki-Karasaki M, Uchida M, Ochiai T (2014a) Depolarization controls TRAIL-sensitization and tumor-selective killing of Cancer cells: crosstalk with ROS. Front Oncol 4:128

    Article  PubMed  PubMed Central  Google Scholar 

  • Suzuki-Karasaki M, Ochiai T, Suzuki-Karasaki Y (2014b) Crosstalk between mitochondrial ROS and depolarization in the potentiation of TRAIL-induced apoptosis in human tumor cells. Int J Oncol 44:616–628

    Article  CAS  PubMed  Google Scholar 

  • Tochigi M, Inoue T, Suzuki-Karasaki M, Ochiai T, Ra C, Suzuki-Karasaki Y (2013) Hydrogen peroxide induces cell death in human TRAIL-resistant melanoma through intracellular superoxide generation. Int J Oncol 42:863–872

    Article  CAS  PubMed  Google Scholar 

  • Toyokuni S, Okamoto K, Yodoi J, Hiai H (1995) Persistent oxidative stress in cancer. FEBS Lett 358:1–3

    Article  CAS  PubMed  Google Scholar 

  • Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8:579–591

    Article  CAS  PubMed  Google Scholar 

  • Trapp V, Lee K, Donate F, Mazar AP, Fruehauf JP (2009) Redox-related antimelanoma activity of ATN-224. Melanoma Res 19:350–360

    Article  CAS  PubMed  Google Scholar 

  • Trinei M, Giorgio M, Cicalese A, Barozzi S, Ventura A, Migliaccio E et al (2002) A p53-p66Shc signalling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene 21:3872–3878

    Article  CAS  PubMed  Google Scholar 

  • Tu BP, Weissman JS (2004) Oxidative protein folding in eukaryotes: mechanisms and consequences. J Cell Biol 164:341–346

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tuma RS (2008) Reactive oxygen species may have antitumor activity in metastatic melanoma. J Natl Cancer Inst 100:11–12

    Article  PubMed  Google Scholar 

  • Upadhyay D, Chang W, Wei K, Gao M, Rosen GD (2007) Fibroblast growth factor-10 prevents H2O2-induced cell cycle arrest by regulation of G1 cyclins and cyclin dependent kinases. FEBS Lett 581:248–252

    Article  CAS  PubMed  Google Scholar 

  • Uren RT, Dewson G, Bonzon C, Lithgow T, Newmeyer DD, Kluck RM (2005) Mitochondrial release of pro-apoptotic proteins: electrostatic interactions can hold cytochrome c but not Smac/DIABLO to mitochondrial membranes. J Biol Chem 280:2266–2274

    Article  CAS  PubMed  Google Scholar 

  • Van Houten B, Hunter SE, Meyer JN (2016) Mitochondrial DNA damage induced autophagy, cell death, and disease. Front Biosci 21:42–54

    Article  Google Scholar 

  • Vance JE (2014) MAM (mitochondria-associated membranes) in mammalian cells: lipids and beyond. Biochim Biophys Acta 1841:595–609

    Article  CAS  PubMed  Google Scholar 

  • Vandewynckel YP, Laukens D, Geerts A, Bogaerts E, Paridaens A, Verhelst X et al (2013) The paradox of the unfolded protein response in cancer. Anticancer Res 33:4683–4694

    CAS  PubMed  Google Scholar 

  • Vercammen D, Brouckaert G, Denecker G, Van de Craen M, Declercq W, Fiers W et al (1998) Dual signaling of the Fas receptor: initiation of both apoptotic and necrotic cell death pathways. J Exp Med 188:919–930

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verfaillie T, Rubio N, Garg AD, Bultynck G, Rizzuto R, Decuypere JP et al (2012) PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress. Cell Death Differ 19:1880–1891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE et al (2000) Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins. Cell 102:43–53

    Article  CAS  PubMed  Google Scholar 

  • Vilema-Enriquez G, Arroyo A, Grijalva M, Amador-Zafra RI, Camacho J (2016) Molecular and cellular effects of hydrogen peroxide on human lung cancer cells: potential therapeutic implications. Oxidative Med Cell Longev 2016:1908164

    Article  Google Scholar 

  • Vousden KH, Lane DP (2007) p53 in health and disease. Nat Rev Mol Cell Biol 8:275–283

    Article  CAS  PubMed  Google Scholar 

  • Wan J, Cui J, Wang L, Wu K, Hong X, Zou Y et al (2018) Excessive mitochondrial fragmentation triggered by erlotinib promotes pancreatic cancer PANC-1 cell apoptosis via activating the mROS-HtrA2/Omi pathways. Cancer Cell Int 18:165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang L, Azad N, Kongkaneramit L, Chen F, Lu Y, Jiang BH et al (2008) The Fas death signaling pathway connecting reactive oxygen species generation and FLICE inhibitory protein down-regulation. J Immunol 180:3072–3080

    Article  CAS  PubMed  Google Scholar 

  • Wangpaichitr M, Wu C, You M, Maher JC, Dinh V, Feun LG et al (2009) N′,N′-dimethyl-N′,N′-bis(phenylcarbonothioyl) propanedihydrazide (Elesclomol) selectively kills cisplatin resistant lung cancer cells through Reactive Oxygen Species (ROS). Cancer 1:23–38

    Article  CAS  Google Scholar 

  • Watanabe T, Sekine S, Naguro I, Sekine Y, Ichijo H (2015) Apoptosis signal-regulating kinase 1 (ASK1)-p38 pathway-dependent cytoplasmic translocation of the orphan nuclear receptor NR4A2 is required for oxidative stress-induced necrosis. J Biol Chem 290:10791–10803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiedemann N, Meisinger C, Pfanner N (2009) Cell biology. Connecting organelles. Science 325:403–404

    Article  PubMed  Google Scholar 

  • William WN Jr, Zinner RG, Karp DD, Oh YW, Glisson BS, Phan SC et al (2007) Phase I trial of motexafin gadolinium in combination with docetaxel and cisplatin for the treatment of non-small cell lung cancer. J Thoracic Oncol 2:745–750

    Article  Google Scholar 

  • Woo SH, Park IC, Park MJ, Lee HC, Lee SJ, Chun YJ et al (2002) Arsenic trioxide induces apoptosis through a reactive oxygen species-dependent pathway and loss of mitochondrial membrane potential in HeLa cells. Int J Oncol 21:57–63

    CAS  PubMed  Google Scholar 

  • Xin-Eng Huang DW, Yang Y-N, Chen S-Q, Zhu M, Zhang X-M, Yu J (2016) MPTP related mitochondrial pathway in oroxylin a induced-apoptosis in HepG2 cancer cells. Int J Clin Exp Pathol 9:11139–11148

    Google Scholar 

  • Xiong Y, Uys JD, Tew KD, Townsend DM (2011) S-glutathionylation: from molecular mechanisms to health outcomes. Antioxid Redox Signal 15:233–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yi X, Yin XM, Dong Z (2003) Inhibition of bid-induced apoptosis by Bcl-2. tBid insertion, Bax translocation, and Bax/Bak oligomerization suppressed. J Biol Chem 278:16992–16999

    Article  CAS  PubMed  Google Scholar 

  • Zeeshan HM, Lee GH, Kim HR, Chae HJ (2016) Endoplasmic reticulum stress and associated ROS. Int J Mol Sci 17:327

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang XY, Yang SM, Zhang HP, Yang Y, Sun SB, Chang JP et al (2015) Endoplasmic reticulum stress mediates the arsenic trioxide-induced apoptosis in human hepatocellular carcinoma cells. Int J Biochem Cell Biol 68:158–165

    Article  PubMed  Google Scholar 

  • Zhang J, Wang X, Vikash V, Ye Q, Wu D, Liu Y et al (2016) ROS and ROS-mediated cellular signaling. Oxidative Med Cell Longev 2016:4350965

    Article  Google Scholar 

  • Zhang R, Li G, Zhang Q, Tang Q, Huang J, Hu C et al (2018) Hirsutine induces mPTP-dependent apoptosis through ROCK1/PTEN/PI3K/GSK3beta pathway in human lung cancer cells. Cell Death Dis 9:598

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhong H, Yin H (2015) Role of lipid peroxidation derived 4-hydroxynonenal (4-HNE) in cancer: focusing on mitochondria. Redox Biol 4:193–199

    Article  CAS  PubMed  Google Scholar 

  • Zhong H, Xiao M, Zarkovic K, Zhu M, Sa R, Lu J et al (2017) Mitochondrial control of apoptosis through modulation of cardiolipin oxidation in hepatocellular carcinoma: a novel link between oxidative stress and cancer. Free Radic Biol Med 102:67–76

    Article  CAS  PubMed  Google Scholar 

  • Zhuang S, Lynch MC, Kochevar IE (1999) Caspase-8 mediates caspase-3 activation and cytochrome c release during singlet oxygen-induced apoptosis of HL-60 cells. Exp Cell Res 250:203–212

    Article  CAS  PubMed  Google Scholar 

  • Zhuang S, Demirs JT, Kochevar IE (2000) p38 mitogen-activated protein kinase mediates bid cleavage, mitochondrial dysfunction, and caspase-3 activation during apoptosis induced by singlet oxygen but not by hydrogen peroxide. J Biol Chem 275:25939–25948

    Article  CAS  PubMed  Google Scholar 

  • Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94:909–950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zou H, Li Y, Liu X, Wang X (1999) An APAF-1.Cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9. J Biol Chem 274:11549–11556

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported in part by grants from the CIHR (MOP-123400) and NSERC (RGPIN/06270-2019) to KYL and an Alberta Cancer Foundation graduate studentship to SN.

Conflicts of Interest

The authors declare no conflict of interest.

Authors’ Contributions

SN wrote the draft. JR and KYL revised the manuscript.

Author information

Authors and Affiliations

  1. Department of Cell Biology and Anatomy, Arnie Charbonneau Cancer Institute and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada

    Saranya NavaneethaKrishnan, Jesusa L. Rosales & Ki-Young Lee

Authors
  1. Saranya NavaneethaKrishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jesusa L. Rosales
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ki-Young Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ki-Young Lee .

Editor information

Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA

    Bimal K. Ray

  3. CSIR-Indian Institute of Chemical Biology, Kolkata, India

    Susanta Roychoudhury

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Singapore Pte Ltd.

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

NavaneethaKrishnan, S., Rosales, J.L., Lee, KY. (2022). ROS-Mediated Apoptosis in Cancer. In: Chakraborti, S., Ray, B.K., Roychoudhury, S. (eds) Handbook of Oxidative Stress in Cancer: Mechanistic Aspects. Springer, Singapore. https://doi.org/10.1007/978-981-15-9411-3_48

Download citation

Publish with us

Policies and ethics

Search

Navigation